A piggyBac transposon-based mutagenesis system for the fission yeast Schizosaccharomyces pombe

The TTAA-specific transposon piggyBac (PB), originally isolated from the cabbage looper moth, Trichoplusia ni, has been utilized as an insertional mutagenesis tool in various eukaryotic organisms. Here, we show that PB transposes in the fission yeast Schizosaccharomyces pombe and leaves almost no footprints. We developed a PB-based mutagenesis system for S. pombe by constructing a strain with a selectable transposon excision marker and an integrated transposase gene. PB transposition in this strain has low chromosomal distribution bias as shown by deep sequencing-based insertion site mapping. Using this system, we obtained loss-of-function alleles of klp5 and klp6, and a gain-of-function allele of dam1 from a screen for mutants resistant to the microtubule-destabilizing drug thiabendazole. From another screen for cdc25-22 suppressors, we obtained multiple alleles of wee1 as expected. The success of these two screens demonstrated the usefulness of this PB-mediated mutagenesis tool for fission yeast

A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

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Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

A preliminary investigation on cross-foldable design in 4D printing

In 4D printing, a printed smart structure would fold or unfold upon an external stimulus. In prior research, the hinges in the smart structure always fold or unfold individually with no crossing or overlap. The design complexity of the smart structure is increased by increasing the total number of hinges. In this research, cross-folding is investigated. Here cross-folding is defined as two overlapping folds in a single hinge. In particular, this research investigates the effect of thickness on cross-folding smart structures. It is found that hinge thickness affects the repeatability of cross-folding. A hinge with a thickness of 0.5 mm could be cross-folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be cross-folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be cross-folded without cracking. The introduction of a physical hole in the centre of the folding/unfolding line provided stress relief and prevented fracture.NRF (Natl Research Foundation, S’pore)Published versio

Design and 3D Printing of Scaffolds and Tissues

A growing number of three-dimensional (3D)-printing processes have been applied to tissue engineering. This paper presents a state-of-the-art study of 3D-printing technologies for tissue-engineering applications, with particular focus on the development of a computer-aided scaffold design system; the direct 3D printing of functionally graded scaffolds; the modeling of selective laser sintering (SLS) and fused deposition modeling (FDM) processes; the indirect additive manufacturing of scaffolds, with both micro and macro features; the development of a bioreactor; and 3D/4D bioprinting. Technological limitations will be discussed so as to highlight the possibility of future improvements for new 3D-printing methodologies for tissue engineering

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work.NRF (Natl Research Foundation, S’pore)Published versio

A feed-centric hypoglycaemia pathway ensures appropriate care escalation in at-risk infants

Background: There is a lack of clarity of what constitutes the starting point of a clinical pathway for infants at-risk of hypoglycaemia. Glucose-centric pathways (GCP) identify low glucose in the first 2 hours of life that may not represent clinical hypoglycaemia and can lead to inappropriate glucose management with infusions and medications. Objective: To study the impact of a feed-centric pathway (FCP) on the number of admissions for hypoglycaemia to level 2 special care nursery (SCN) and the need for parenteral glucose/medications, compared to GCP. Methods: This project was conducted over 2 years, before and after switching from a GCP to FCP in our institution. FCP involves skin-to-skin care, early breast feeding, checking glucose at 2 hours and use of buccal glucose. The primary outcome was the number of SCN admissions for hypoglycaemia. Secondary outcomes include the number of infants needing intravenous glucose, medications and length of SCN stay. Results: Of 23 786 live births, 4438 newborns were screened. We screened more infants at-risk for hypoglycaemia using the FCP (GCP:1462/11969, 12.2% vs FCP:2976/11817, 25.1%) but significantly reduced SCN admissions (GCP:246/1462, 16.8% vs FCP:102/2976, 3.4%; p<0.0001). Fewer but proportionally more FCP newborns required intravenous glucose (GCP: 136/246, 55% vs FCP: 88/102, 86%; p=0.000). Compared with GCP, FCP reduced the total duration of stay in SCN by 104 days per annum, reducing the cost of care. However, the mean length of SCN stay for FCP was higher (GCP:2.43 days vs FCP:3.49 days; p=0.001). There were no readmissions for neonatal hypoglycaemia to our institution. Conclusion: The use of FCP safely reduced SCN admissions, averted avoidable escalation of care and helped identify infants who genuinely required intravenous glucose and SCN care, allowing more efficient utilisation of healthcare resources.Published versio

3D printing of smart materials: a review on recent progresses in 4D printing

Additive manufacturing (AM), commonly known as three-dimensional (3D) printing or rapid prototyping, has been introduced since the late 1980s. Although a considerable amount of progress has been made in this field, there is still a lot of research work to be done in order to overcome the various challenges remained. Recently, one of the actively researched areas lies in the additive manufacturing of smart materials and structures. Smart materials are those materials that have the ability to change their shape or properties under the influence of external stimuli. With the introduction of smart materials, the AM-fabricated components are able to alter their shape or properties over time (the 4th dimension) as a response to the applied external stimuli. Hence, this gives rise to a new term called ‘4D printing’ to include the structural reconfiguration over time. In this paper, recent major progresses in 4D printing are reviewed, including 3D printing of enhanced smart nanocomposites, shape memory alloys, shape memory polymers, actuators for soft robotics, self-evolving structures, anti-counterfeiting system, active origami and controlled sequential folding, and some results from our ongoing research. In addition, some research activities on 4D bio-printing are included, followed by discussions on the challenges, applications, research directions and future trends of 4D printing